The role of hyperglycaemia in the pathogenesis of hypotension in diabetic disorders was investigated using the changes in cardiac M 2-muscarinic receptor (M 2-mAChR) gene expression in type-1-like diabetic rats and cultured cardiomyocytes. Blood pressure was markedly decreased in diabetic rats following the intravenous injection of streptozotocin (STZ) for 8 weeks. Also, the baroreflex sensitivity (ΔHR/ΔBP), as measured by the changes in heart rate (ΔHR) and mean blood pressure (ΔBP) 1 min after the intravenous injection of phenylephrine (10 μg/kg), was significantly increased. Arecaidine propargyl ester (APE), a M 2-mAChR agonist produced a marked reduction in heart rate in these diabetic rats. Normalization of plasma glucose in diabetic rats using insulin (0.5 IU) or phlorizin (1 mg/kg) injection attenuated the blood pressure reduction and reversed the mRNA and protein levels of cardiac M 2-mAChR. A high concentration of glucose (20 mmol/l) directly influenced the increase in gene expression of M 2-mAChR in the H9c2 cardiac cell line. Hyperglycaemia induced an increase in cardiac M 2-mAChR gene expression, suggesting a role in the pathogenesis of hypotension in diabetic disorders.
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